Fewer Bacterial Relapses after Oral Treatment with Norfloxacin than with Ceftibuten in Acute Pyelonephritis Initially Treated with Intravenous Cefuroxime

Abstract

This double-blind, multicentre study was performed at nine centres on a total of 171 patients who presented with fever (> 38.5 degrees C) and signs of acute pyelonephritis. All were initially treated with intravenous cefuroxime. After 2-3 d, when the fever had subsided and urinary culture had revealed growth of Gram-negative bacteria ( > 10(7) colony-forming units per litre), treatment was changed to oral administration of ceftibuten 200 mg b.i.d. or norfloxacin 400 mg b.i.d. for 10 d. The patients were followed for signs of bacterial or clinical relapse 7-14 d after the end of treatment. The initial clinical and bacteriological cure was excellent in both groups, but there were significantly fewer bacterial relapses after oral treatment with norfloxacin than with ceftibuten in acute febrile pyelonephritis initially treated with intravenous cefuroxime. The causal strain was eradicated in 75% of patients (73% of males, 76% of females) in the ceftibuten group and in 89% of patients (94% of males, 85% of females) in the norfloxacin group. The relative frequency of eradication was 0.84 (p < 0.05; 95%, confidence interval 0.74-0.97). Adverse events were reported by 47% of the patients in the ceftibuten group and by 38% in the norfloxacin group. This difference was not significant, but diarrhoea or loose stools occurred more frequently in the ceftibuten group.

Treatment Duration of Febrile Urinary Tract Infections

“…The same results in men were obtained from a third Swedish trial, [20] which used step-down treatment; initial intravenous treatment with cefuroxime was followed by either norfloxacin 400 mg twice daily or ceftibuten 200 mg twice daily for 10 days. Thus, these studies provided evidence that men with mild to moderate febrile UTI may be safely treated at home with a 14 days regimen of an oral fluoroquinolone.…”

“…The data from Cronberg et al [20] suggest inferior microbiological efficacy of oral cephalosporins compared with the fluoroquinolones, consistent with another Swedish study [24]. To our knowledge, there are no published studies on the efficacy of amoxicillin-clavulanate in the treatment of febrile UTI compared to trimethoprim-sulfamethoxazole or a fluoroquinolone.…”

“…Subgroup analysis of data about acute pyelonephritis [18] lend additional support that an oral 5-day regimen of a once-daily fluoroquinolone (levofloxacin 750 mg) or a 10-day regimen of ciprofloxacin 500 mg twice daily (in 6.1% after initial intravenous ciprofloxacin 400 mg twice daily) might be effective for mild to moderate febrile UTI, even in those with bacteremia or complicating factors like obstruction or presence of a urinary catheter. Another pyelonephritis study in hospitalized men and women [20], prospectively comparing 10 days of norfloxacin 400 mg twice daily with 10 days of ceftibuten 200 mg twice daily, after receiving intravenous cefuroxime for 2–4 days in each group prior to randomization to the study drug, showed excellent clinical and bacteriological cure rates in both groups and lower bacterial relapse rates in patients treated with norfloxacin. The finding that a 1 week regimen of fluoroquinolones is both efficacious and safe for treatment of mild to moderate febrile UTI was further supported by a randomized comparative study demonstrating similar outcomes in comparing levofloxacin 250 mg once daily, ciprofloxacin 500 mg twice daily and lomefloxacin 400 mg once daily, although in severe, invasive infections such a low dose of levofloxacin may result in marginal tissue and blood concentrations [21].…”

“…When the uropathogen is susceptible, current evidence support a 14-day regimen [17]; shorter treatment duration has never been well investigated. Oral β-lactams are likely less effective compared with fluoroquinolones and trimethoprim-sulfamethoxazole [15, 20, 24, 25]. When used, a total course of 10–14 days of therapy is recommended [4, 9, 10•, 26].…”

“…Trimethoprim also achieves adequate concentrations in the prostate and is an alternative to fluoroquinolones provided the bacteria are susceptible to this antimicrobial [31]. As described earlier in this article and demonstrated in some mixed trials with a minority of men, therapy with β-lactams may result in lower cure rates in men with febrile UTI [20, 24]. …”